Studies on the biochemical effect of drugs in animals and man using mass spectral methodology are being pursued in order to relate pharmacological action to molecular events and clinical efficacy. Work in progress includes the synthesis of stable isotope labeled compounds for kinetic studies in man of neurotransmitters (catecholamine derivatives) and the effects of various drugs upon the synthesis and release of catecholamines. Drug manipulation of melatonin levels is being measured to indicate beta-adrenergic receptor activity. Tricyclic antidepressants (imipramine, desipramine) and their hydroxylated metabolites are being quantitated from patients by mass spectral measurements in order to establish therapeutic and predictive indices.